TdT: Definition

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TdT, short for terminal deoxynucleotidyl transferase, is a protein found in the nucleus of very young, immature lymphocytes. Pathologists test for TdT to help diagnose acute lymphoblastic leukemia and lymphoblastic lymphoma, which are cancers made of these immature cells. TdT also helps the pathologist diagnose thymoma, a tumor of the thymus gland in the chest.

This article explains what TdT is, which cells carry it, how pathologists use it to diagnose cancer, and what a TdT result in your pathology report means.

What is TdT?

TdT is an enzyme that helps young lymphocytes build their antigen receptors, the molecules that let each immune cell recognize a different germ. It works by adding small, random building blocks to the genes for these receptors, which makes every new lymphocyte slightly different. Once a lymphocyte matures, it switches off TdT. In healthy people, TdT appears mostly in two places:

Bone marrow. Young B cells that are still developing in the bone marrow carry TdT for a short time.
Thymus. Young T cells, called thymocytes, carry TdT while they mature inside the thymus gland.

How do pathologists test for TdT?

Pathologists test for TdT using immunohistochemistry, a test that uses antibodies to find specific proteins in a thin slice of tissue. Cells that carry TdT show a brown color inside the nucleus under the microscope. Laboratories can also measure TdT on blood or bone marrow cells with flow cytometry, which is often part of the first tests for a new leukemia.

How does TdT help diagnose leukemia and lymphoma?

TdT helps diagnose leukemia and lymphoma because it marks cancer cells that came from immature lymphocytes. Pathologists call these cancer cells lymphoblasts, and they are TdT-positive in most cases of lymphoblastic leukemia and lymphoblastic lymphoma. Doctors call the same disease leukemia when it is mainly in the blood and bone marrow and lymphoma when it mainly forms a mass. The main examples include:

B-lymphoblastic leukemia and lymphoma. These cancers come from young B cells and include B-lymphoblastic leukemia and B-lymphoblastic lymphoma.
T-lymphoblastic leukemia and lymphoma. These cancers come from young T cells and include T-cell acute lymphoblastic leukemia and T-lymphoblastic lymphoma.

TdT is especially useful because lymphoblasts can look like other small, round cancer cells under the microscope. Lymphomas made of mature cells, such as Burkitt lymphoma and mantle cell lymphoma, are TdT-negative. A positive TdT result in the abnormal cells therefore points strongly toward a lymphoblastic cancer.

How does TdT help diagnose thymoma?

TdT helps diagnose thymoma because many thymomas contain large numbers of young, normal T cells mixed in with the tumor cells. These young T cells are TdT-positive, even though the tumor cells themselves are not. Thymic carcinoma, a more serious tumor of the thymus, usually lacks these young T cells, so TdT helps the pathologist distinguish the two.

The young T cells in a thymoma can also be confusing, because a small biopsy full of TdT-positive cells may look like T-lymphoblastic lymphoma. The pathologist uses the appearance of the tumor and other markers, such as cytokeratins, to make the correct diagnosis.

Where else might TdT be positive?

TdT is mainly a marker of immature lymphocytes, but a few other cancers can also be positive. Merkel cell carcinoma, a type of skin cancer, is positive for TdT in many cases. A small number of acute myeloid leukemias are also positive. For this reason, the pathologist always interprets TdT together with other markers rather than on its own.

What does a TdT result mean in my report?

A TdT result in your report describes whether the cells being studied contain this protein. Your report may describe the result in one of several ways:

Positive. The abnormal cells contain TdT, which supports a diagnosis of lymphoblastic leukemia or lymphoblastic lymphoma when the other markers fit.
Negative. The abnormal cells do not contain TdT, which points toward a cancer made of more mature cells or a different type of tumor.
Positive in background T cells. In a thymus tumor, the positive cells are young, normal T cells mixed in with the tumor, which supports a diagnosis of thymoma.

Questions to ask your doctor

Were the abnormal cells in my sample positive or negative for TdT?
Which other markers did the pathologist test along with TdT?
Do I have leukemia, lymphoma, or another type of tumor?
Did the abnormal cells come from B cells or T cells?
Was flow cytometry done on my blood or bone marrow?
If I have a thymus tumor, is it a thymoma or a thymic carcinoma?
Will I need a bone marrow biopsy or genetic tests?